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Design, Synthesis, And Pharmacological Evaluation Of Three Series Of Lobelane Analogs As Inhibitors Of The Vesicular Monoamine Transporter (Vmat2), John P. Culver

Theses and Dissertations--Pharmacy

Methamphetamine (METH) abuse is a serious problem in the United States and worldwide. The reward experienced by METH users is due to the increase in extracellular dopamine (DA) concentrations caused by an interaction between METH and the DA transporter (DAT) as well as the Vesicular Monoamine Transporter-2 (VMAT2). The reward felt by users of METH leads to further use of the drug and subsequent abuse. The current project examined the ability of three novel series of lobelane analogs to interact with a binding site on the Vesicular Monoamine Transporter-2 (VMAT2) in an attempt to inhibit the effects of METH. Lobelane …

Chemoenzymatic Studies To Enhance The Chemical Space Of Natural Products, Jhong-Min Chen

Theses and Dissertations--Pharmacy

Natural products provide some of the most potent anticancer agents and offer a template for new drug design or improvement with the advantage of an enormous chemical space. The overall goal of this thesis research is to enhance the chemical space of two natural products in order to generate novel drugs with better in vivo bioactivities than the original natural products.

Polycarcin V (PV) is a gilvocarcin-type antitumor agent with similar structure and comparable bioactivity with the principle compound of this group, gilvocarcin V (GV). Modest modifications of the polyketide-derived tetracyclic core of GV had been accomplished, but the most …

Triphenylamine-, Porphyrin- And Fullerene-Based Derivatives For Photovoltaic And Other Applications, Danisha Marie Rivera Nazario

Open Access Theses & Dissertations

Proper collection of charges at the electrodes is an important process in organic solar cells. Interfacial layers between the electrodes and the photoactive layer have been design to improve charge collection and ohmic contacts. The most studied interfacial layer between the anode and the photoactive layer is the negatively charged polymer poly(3,4-ethylendioxythiophene):poly(styrenesulfonate) (PEDOT:PSS), that possesses good hole transporting ability. However, inhomogeneities at the surface of the electrode after deposition of the polymer lower the stability and performance of the OPV devices. Triphenylamine (TPA) derivatives have received increased attention in the organic solar cells (OSCs) field because of their favorable light …

On The Catalytic Activity Of Palladium Nanoparticles-Based Anodes Towards Formic Acid Electro-Oxidation: Effect Of Electrodeposition Potential, Islam M. Al-Akraa Dr., Ahmad M. Mohammad Prof, Mohamed S. El-Deab Prof, Bahgat E. El-Anadouli Prof

Chemical Engineering

In this investigation, the catalytic activity of palladium nanoparticles (PdNPs)-modified glassy carbon (GC) (simply noted as PdNPs/GC) electrodes towards the formic acid electro-oxidation (FAO) was investigated. The deposition of PdNPs on the GC substrate was carried out by a potentiostatic technique at different potentials and the corresponding influence on the particles size and crystal structure of PdNPs as well as the catalytic activity towards FAO was studied. Scanning electron microscopy (SEM) demonstrated the deposition of PdNPs in spherical shapes and the average particle size of PdNPs deposited at a potential of 0 V vs. Ag/AgCl/KCl(sat.) was the smallest (ca. 8 …

Transition Metal Catalysis And The Synthesis Of Biologically Interesting Heterocycles: A Study Of Gold-Catalyzed Intermolecular Cyclization And Palladium-Catalyzed Suzuki Cross-Coupling, Alexandria E. Weber

Undergraduate Honors Thesis Projects

Two methods of transition metal catalysis were investigated as a means to synthesize biologically interesting heterocyclic molecules. The gold-catalyzed intermolecular cyclization of allenes and 1,3-dipoles was first explored. An allene, ethyl-3-hexyl-3,4-pentadienoate was subjected to a combination of one of five 1,3-dipoles ((Z)-N-benzylidenemethanamine oxide, 1-benzylidene-3-oxopyrazolidin-1-ium-2-ide, (Z)-N-benzylidenebenzenamine oxide, (E)-N-benzylidenebenylamine, and (E)-N-Benzylidene-4-methoxybenzenamine) and one of three gold catalysts (1,3-bis(2,6-di-isopropylphenyl)imidazole-2-ylidenegold(I)chloride, chlorotriphenyl-phosphinegold(I), and gold(III) chloride). No heterocyclic product resulted from these catalytic reactions. The palladium-catalyzed Suzuki cross-coupling reaction of a 1,3,4-oxadiazole (3-(5-(4-(bromo)phenyl)-1,3,4-oxadiazol-2-yl)pyrazine-2-amine) with phenyl boronic pinacol ester was then explored, varying whether the 1,3,4-oxadiazole was unprotected or …

Investigating The Synthesis Of Heterocycles Via Gold Catalyzed Cyclizations And Cyclo-Dehydrating Reactions, Katherine L. Childers

Undergraduate Honors Thesis Projects

The goal of this project was to study novel synthetic procedures for heterocycles. This was achieved through a two-part investigation. In the first part, a variety of conditions for the gold catalyzed cyclization of allenes were studied. This work was focused on the lesser studied intermolecular reactions of allenes. A variety of allenes were synthesized, and then reacted with 1,3-dipoles and a gold catalyst. These reactions were determined to be unsuccessful through the analysis of nuclear magnetic resonance spectroscopy data. In the second part of this study, the synthesis of 1,3,4-oxadiazoles was investigated. Several cited procedures were examined to determine …

Exploration Of Materials Used In 3-Dimensional Printing For The Dental Industry, Holly Chang Hayden

Scripps Senior Theses

A limiting factor in the digitization of dental devices is the availability of materials suitable for use in both dentistry and the new digital technologies. As a rapidly growing industry, three-dimensional printing (3DP) has the potential to disrupt traditional manufacturing and prototyping methods. A review of both restorative materials and the current 3DP materials has lead to a focus on fiber- reinforced composites in the exploration for a new 3DP material. In addition, another area worth exploring and investing in would be 3D bioprinting as it opens up the possibility of regenerative dentistry.

Sharp Rna Recognition Motif Optimizations, Extensions, And Mutations For Use In 2d And 3d Nmr Experiments, Shaun M. Christie

Williams Honors College, Honors Research Projects

SMRT/HDAC Associated Repressor Protein interacts with the long noncoding RNA, produced by SRA, by binding at the RRMs. Three projects were done to prepare the truncated proteins for use in 2D and 3D NMR experiments. The first focuses on RRM 3 and its optimization during the purification process. The second focuses on RRM 2-4, which was found to be missing two alpha helices that may be important for protein stability. These helices can also interact with RRM 3 as well due to the tight association of RRMs 3 and 4. The two step PCR extension of RRM 2-4 was assumed …

Boron Functionalization Of Bodipy Dyes, And Their Evaluation As Bioimaging Agents, Alex Long Nguyen

LSU Doctoral Dissertations

BODIPY, also known as “porphyrin’s little sister,” belongs to a class of fluorescent dyes. It contains a dipyrromethene π-system with a disubstituted boron atom. The basic 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) is known for its numerous useful applications in the fields of biology and materials. Modification of this well-known fluorophore has been shown to change its photophysical and chemical properties. There has been great interest in the modification at the boron center in recent years for synthesizing new dyads and cascade-type dyes. This work focuses on functionalization at the boron center with carbon and oxygen nucleophiles for further investigation as bioimaging agents. Chapter …

I. Synthesis Of Ascarosides For Biological Evaluation And Ii. Development Of Visible Light-Promoted Selenofunctionalization And Grafting Of Aryl Iodides, Elizabeth Susan Conner Balapitiya

LSU Doctoral Dissertations

This dissertation focuses on analog synthesis for biological evaluation and visible light promoted method development. Chapter 1 centers upon the synthesis of Caenorhabditis elegans dauer pheromone analogs. C. elegans is a nematode which, in times of environmental stress, enters a dauer stage. Two highly conserved pathways, which play important roles in some diseases in higher organisms, monitor dauer formation: TGF-β and IGF-1. Dauer formation is triggered by the nematode’s chemosensation of the dauer pheromone, consisting of a group of previously-isolated ascarosides. These compounds differ in chain length, saturation, terminal functionality of side chain, ω vs. ω-1 oxygenation and presence of …

Expression And Characterization Of Mouse Notch1 Abruptex Egf Repeats In E. Coli, Amid Paudyal

LSU Master's Theses

Notch1 is a transmembrane protein involved in cell signaling, which is found to be linked to various genetic and neurodegenerative diseases. The extracellular domain of the Notch1 protein consists of 36 tandem epidermal growth factor-like (EGF) repeats, which are directly involved in ligand binding and are heavily glycosylated. EGF 24-29 repeats lie in the Abruptex region of the Notch1 protein, and regulate the ligand binding activity through structural changes. The role of glycosylation in ligand binding events and the overall structure of the Abruptex region are not known. Also, the role of calcium binding in Notch activation or inhibition is …

Development Of New Linking Chemistry With The Fac-{Re(Co)3}+ Core For Eventual Applications In Radiopharmaceuticals In Imaging And Therapy, Aponsu Meregngna Pramuditha Lakmi Abhayawardhana

LSU Doctoral Dissertations

The facile labeling of biomolecules with a radionuclide is a key goal in radiopharmaceutical development. This study explores two different ligand systems for fac-[Re(CO)3L]+ complexes, that could be used in bioconjugation. The first approach uses a tridentate ligand having a sulfonamide linkage and modeled on previously evaluated fac-[Re(CO)3(N(SO2R)dpa)]PF6 complexes. The present goal was to develop new related sulfonamide complexes with more hydrophilic ligands designed to avoid the bioavailability problems that would plague the N(SO2R)dpa ligand system. A series of fac-[Re(CO)3(N(SO2R)dien)]PF6 complexes with different R groups linked to the central nitrogen of a symmetric tridentate sulfonamides were synthesized with the aim …

Photoelectrons And Recombining Electrons In Atomic And Molecular Systems, Kristen D'Ann Fulfer

LSU Doctoral Dissertations

This work in this dissertation explores how photoelectrons enter and exit atoms and molecules. The electron rescattering events which may occur during photoionization or photorecombination processes play a dominant role in the understanding of how photoelectrons enter and exit molecules, which is intrinsically linked to how chemical reactions occur. Chapters 3-4 of this dissertation present evidence of vibrational mode specific breakdown of the Franck-Condon Principle in the photoionization of low symmetry molecules, acrolein and the singly halogenated thiophenes, due to resonant and non-resonant electron rescattering dynamics. In Chapters 5-6, the disentanglement of the valence electronic structure, as well as evidence …

Scanning Probe Investigations Of Nanopatterned And Thermo-Responsive Polypeptoids And The Design Of A Sample Stage For Force Modulation Microscopy, Lu Lu

LSU Doctoral Dissertations

Protocols for patterning nanostructures of polymers were developed to enable scanning probe microscopy (SPM) studies of surface properties at the molecular level. A chemically selective surface for patterning polymers was generated by combining particle lithography with organosilane immersion. Poly(N-allyl glycine), a biocompatible and backbone degradable polypeptoid, was grown on Si(111) at confined amine sites using surface-initiated polymerization (also known as the “graft from” approach). A thermo-responsive random copolypeptoid, poly[(N-ethyl glycine)32-r-(N-butyl glycine17)], was pre-synthesized and attached onto a patterned organosilane surface using a thiol-ene click reaction (“graft to” approach). The phase transitions of the copolypeptoid nanostructures in an aqueous environment was …

The Electronic Structure Of Environmentally Persistent Free Radicals Formed On Metal Oxide Surfaces, Chad Allen Thibodeaux

LSU Doctoral Dissertations

We have investigated the electronic structure of environmentally persistent free radicals (EPFRs) formed on two different metal oxides: Cu(II)O and ZnO. Cu(II)O is known to be one of the most active metal oxides to form EPFRs. ZnO, however, forms the longest-lived EPFRs. First, we examined the adsorption of phenol on different crystal faces of ZnO. Ultraviolet photoelectron spectroscopy (UPS) shows direct evidence of charge transfer away from the ZnO to the phenol. This differs from the hypothesized mechanism of EPFR formation that says that an electron is transferred to the metal oxide. UPS difference spectra also shows that the phenol …

Method Development For The Assignment Of Nmr Peaks And The Determination Of Quaternary Protein Structure Using Reductive Methylation, Pamlea Nicole Brady

LSU Doctoral Dissertations

The work described herein is centered on reductive methylation, a chemical modification reaction, which allows for the introduction of methyl groups at the primary amines of the lysine side chain and at the N-terminus. The resulting methyl groups are effective probes for the study of protein structure and dynamics using nuclear magnetic resonance spectroscopy (NMR). Described herein is work conducted on the development of tools for the study of protein structure using reductive methylation, highlighting options for addressing limitations of the labeling method encountered by its practical use. Chapter 1 serves as a brief introduction to protein structure and the …

Chemically Patterned Surfaces As Test Platforms To Study Magnetic And Solvent-Responsive Properties At The Nanoscale: Investigations Using Scanning Probe Microscopy, Shalaka Kulkarni

LSU Doctoral Dissertations

Chemically patterned surfaces were fabricated using a combination of molecular self-assembly and particle lithography to generate billions of nanostructures of organosilane self-assembled monolayers (SAMs). Monodisperse mesospheres were used as surface masks to prepare nanostructures on flat surfaces using the simple benchtop chemistry steps of mixing, centrifuging, evaporation, and drying. Periodic arrays of well-defined organosilane nanostructures serve as discrete surface sites for the selective deposition of polymers and magnetic nanoparticles.

In this dissertation, particle lithography approaches for surface patterning provide new directions for studying surface chemistry at the molecular-level using high resolution investigations with scanning probe microscopy (SPM). Atomic force microscopy …

Development Of Transition Metal-Catalyzed Polymerization Reactions And Their Applications For The Preparation Of Well-Defined Conjugated Polymer Architectures, Carlos Anthony Chavez

LSU Doctoral Dissertations

The synthesis of conjugated polymers and design of complex materials based on them have become increasingly popular as the demand for low-cost efficient and processible optoelectronic and semiconducting devices escalates. While advanced applications of polymeric materials require some degree of sophistication, success can be achieved through careful consideration of polymerization techniques and methodologies. Controlling critical aspects of the polymerization process allows for synthesis of complex macromolecular architectures possessing unique and novel properties that may be worth of further comprehensive investigation. This dissertation primarily focuses on the development and preparation of well-defined hierarchical macromolecular architectures. The foundation of this work encompasses …

Design And Application Of Task-Specific Organic Salts For Chemical And Biochemical Sensing, Waduge Indika Subodha Galpothdeniya

LSU Doctoral Dissertations

There is an increasing demand for development of new sensors and sensor strategies for accurate detection and discrimination of various analytes. In this regard, colorimetric and fluorometric sensor approaches have attracted considerable attention, primarily because they represent facile and inexpensive analytical tools. In this dissertation, I discuss the design and application of sensors and sensor arrays using task specific organic salts: ionic liquids (ILs) and a group of uniform materials based on organic salts (GUMBOS). As compared to typical ionic compounds, these two classes of organic salts exhibit relatively lower melting points due to bulky organic cations and/or anions. Interestingly, …

Synergistic Properties-Driven Synthesis Of Aluminides, Antiomonides, And Bioceramics, Pilanda Watkins-Curry

LSU Doctoral Dissertations

The synthesis, characterization, and properties of selected intermetallics and ceramic materials are presented in this dissertation. In our quest to grow single crystal intermetallics from the metal flux technique, new strategies were employed to avoid thermodynamically stable phases and to ensure sample homogeneity of the crystalline product for structure elucidation and accurate measurements of their magnetic and electrical properties. The relationship between the complex crystal structures and magnetic properties are reported for LnCo2Al8 (Ln = La-Nd, Sm, Yb), CeCo2-xMnxAl8 (0 < x < 1), and Pr2Fe4-xCoxSb5 (1 ≤ x < 3). The discovery of magnetic frustration in LnCo2Al8 (Ln = Ce, Nd) and complex magnetic ordering coupled with large positive magnetoresistance of up to 150% and 60% at 200 K with relatively low field of H = 1 T in Pr2Fe4-xCoxSb5 (x ≈ 2 and 2.5) is also reported. The demand of new inorganic solid materials as scaffolds for the engineering of bone tissue has led to the synthesis of calcium magnesium silicates such as, diopside (CaMgSi2O6), akermanite (Ca2MgSi2O7), monticellite (CaMgSiO4), and merwinite (Ca3Mg(SiO4)2)) for studying dimensionality and mechanical properties. This dissertation highlights the synergism of solid state chemistry at the interface of condensed matter physics and biological engineering. The discovery of compounds with tunable magnetic, electrical, and mechanical properties will be described herein.

I. Synthesis Of Ascarosides For Chemical Biology Studies In Caenorhabditis Elegans, Ii. A Photochemical Approach To Delavayine, And Iii. Remote Hydroxylation By Radical Translocation And Polar Crossover, Kyle Allen Hollister

LSU Doctoral Dissertations

The foci of this dissertation are the synthesis of analogs for chemical biology studies, synthetic chemistry method development (with an emphasis on photochemistry), and the application of these methods toward total synthesis. Chapter 1 outlines the synthesis of an array of pheromone analogs that are derivatives of the dideoxy sugar ascarylose. Referred to as ascarosides, such compounds have recently been shown to influence important biological processes in the model organism Caenorhabditis elegans. C. elegans secretes ascarosides into its environment, where the compounds then act as signaling molecules by providing information on factors like population density. Chapter 2 describes the biological …

Gumbos As Matrices For Matrix-Assisted Laser Desorption Ionization Time Of Flight Mass Spectrometry, Hashim Abdullah Al Ghafly

LSU Doctoral Dissertations

This work involves the investigation of a group of uniform materials based on organic salts (GUMBOS) as matrices for matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF) for analysis of hydrophobic biomolecules. GUMBOS are new class of materials that show great promise as MALDI matrices because they are able to form a thin-layer on the MS target, thereby enhancing the sample homogeneity, signal intensity, and shot-to-shot reproducibility. The detection of hydrophobic peptides using MALDI-TOF MS remains a challenge because the majority of matrices utilized are hydrophilic thereby exhibiting low affinity for hydrophobic molecules. To address this, I …

Single Molecule Electrophoresis And Optical Detection Using Thermoplastic Nanofluidic Devices: An Experimental And Simulation Study, Kumuditha Madushanka Weerakoon Ratnayake

LSU Doctoral Dissertations

Nanofludic devices provide a great platform for single molecular analysis. The unique phenomena in nanoscale gained such interest in investigating the single molecular behavior in nanochannels. Sizes less than 200 nm in one or two-dimensional structures have lead to fascinating observations not accessible in microscale. When a single molecule translocates through a nanotube it interacts with channel walls by adsorption/ desorption, van der Waals interactions and hydrophilic interactions providing a mechanism for separation without any extra additives. Moreover, double layer thickness governed by the background electrolyte plays a vital role. We report single molecular electrophoresis phenomena in nanochannels and nanoslits …

Synthetic Methods Development Towards The Total Synthesis Of Chlorosulfolipids, Andres Villalpando

LSU Doctoral Dissertations

The focus of this dissertation is the development of a novel chlorination reaction utilizing a triphosgene-amine based mixture towards the total synthesis of chlorosulfolipids, a subclass of naturally occurring organohalogen natural products. This novel, mild chlorination reaction will be utilized under a global chlorination strategy to chlorinate multiple alcohol substituents in one synthetic operation. Chapter one details the history of chlorosulfolipids from the early stages of their isolation, relevant structural elucidation techniques, appropriate biosynthetic discoveries, and their biological relevance to a thorough investigation of the total syntheses completed to date. These compounds demonstrate a range of biological activities and have …

On The Development Of Analytical Methodologies To Interrogate The Lipid Dynamics And Phase Transition Resulting From The Reduction Of Stimuli-Responsive Vesicles, James Edward Winter

LSU Doctoral Dissertations

The potential is great for liposome drug delivery systems that provide specific contents release at diseased tissue sites upon activation by upregulated enzymes; however, this potential will only come to fruition with mechanistic knowledge of the contents release process. NAD(P)H:quinone oxidoreductase type 1 (NQO1) is a target for reductively-responsive liposomes, as it is an enzyme upregulated in numerous cancer tissues and is capable of reducing quinone propionic acid (QPA) trigger groups to hydroquinones that self-cleave from dioleolylphosphatidylethanolamine (DOPE) liposome surfaces, thereby initiating contents release. This research targets the development of analytical methodologies to observe and characterize the dynamics and resulting …

Synthesis, Characterization, And Evaluation Of Small Molecule-Based Fluorogenic Probes For The Detection Of Cellular Thiols, Rasika Ranatunga Nawimanage

LSU Doctoral Dissertations

Fluorescence methods for disease diagnosis and detection of important analytes are becoming popular route as a technique, as they offer a simple non-invasive approach. Recently, many novel fluorophores and probes have been reported for selectively and sensitively detecting low abundance biological species in disease pathways. Biological thiols, such as glutathione, cysteine, and homocysteine, along with the smallest member hydrogen sulfide, are key thiol analytes in biological environments, and they play a vital role in living systems by maintaining the redox homeostasis of cells. Alteration of their ratios can cause cellular dysfunction and cell death. Furthermore, thiol levels in cells and …

Nanoscale Gumbos: Size-Control, Characterization, And Applications As Enantioselective Molecularly Imprinted Polymers And Fluorescent Materials, Suzana Hamdan

LSU Doctoral Dissertations

Nanomaterials derived from a group of uniform materials based on organic salts (GUMBOS) have been introduced into the scientific literature through many analytical, biological, and technological applications. These nanomaterials, referred to as nanoGUMBOS, have been shown to display a number of interesting properties including fluorescence, magnetism, tumor targeting, and optoelectronic properties. Herein, we present major studies on nanoGUMBOS including synthesis and size-control, chiral molecular imprinting in polymers, as well as investigation of optical properties and quantum yield of fluorescent semiconductor-based nanoGUMBOS. Various strategies were introduced for production of well-defined nanoGUMBOS. Specifically, several methods based on sonochemistry, microwave, cyclodextrin, and surfactant-assisted …

Total Synthesis Of Clavatadine A Analogs To Produce A Viable Reversible Inhibitor For Factor Xia, Christopher E. Malmberg

All Master's Theses

Cardiovascular disease has quickly become a major health concern in the United States, with numerous citizens dying from cardiovascular disease each year. Older medications, while effective against cardiovascular disease, are problematic to prescribe. A recently isolated natural product, clavatadine A, selectively inhibits human blood coagulation factor XIa. As a result, the synthesis and biological testing of clavatadine A and synthetic clavatadine A analogues that selectively inhibit factor XIa would represent a new direction in cardiovascular disease research. A potent and selective factor XIa inhibitor has the potential to be a safer replacement for current anticoagulants, such as Warfarin, Pradaxa^{® …}

Identification Of Interactions Between Lhx2 And Other Neocortical Proteins, William Shannon Jackson

All Master's Theses

Lhx2 is a protein that is expressed in a gradient across the developing neocortex and is involved in arealization, the process through which this structure is divided into functional fields. However, little is known on how Lhx2's graded expression across the neocortex actually regulates the locations and sizes of the neocortical areas. In an attempt to understand how Lhx2 performs its functions within the neocortex, a yeast two-hybrid screen was used to identify possible binding partners for Lhx2. Of the sixteen pulled from the screen, two proteins, Eri3 and Ddx50, were deemed as having the highest likelihood of playing a …

Electrochemical Monitoring Of The Interaction Between Mitomycin C And Dna At Chitosan--Carbon Nanotube Composite Modified Electrodes, Pembe Ece Canavar, Ece Ekşi̇n, Kadri̇ye Arzum Erdem Gürsan

Turkish Journal of Chemistry

Single-walled carbon nanotube (CNT) and chitosan composite (chitosan*CNT) based sensors were developed as DNA biosensors, and then they were applied for electrochemical investigation of the interaction between the anticancer drug mitomycin C (MC) and DNA. The oxidation signals of MC and guanine were monitored before and after the interaction process by differential pulse voltammetry (DPV). The DPV results were in good agreement with those of electrochemical impedance spectroscopy (EIS). Analytical parameters such as DNA concentration, MC concentration, and MC interaction time with DNA were optimized. The detection limits were 6.85 \mu g/mL for DNA and 11.01 \mu g/mL for MC.